Allergic Rhinitis and Cancer Risk: A Two-Sample Mendelian Randomization Study.

Background: There is increasing evidence that allergic rhinitis (AR) is associated with cancer. However, these results are inconsistent. Because of common risk factors, there may be reverse causality and confounding factors that affect our understanding of the relationship between AR and cancer. We aimed to explore the role of AR in cancer development using Mendelian randomization (MR) analysis. Materials and Methods: We performed a two-sample MR analysis using summary data from genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) strongly associated with AR (or hay fever) were used as instrumental variables, mainly using the inverse variance weighted analysis method, supplemented by MR Egger, maximum likelihood, weighted media, and penalized weighted media for MR analysis. Sensitivity analyses included heterogeneity and horizontal pleiotropy; and leave-one-out analyses were performed to test the robustness of our results. Results: MR analysis revealed no evidence of a causal relationship between AR and any of the examined cancers (all p > 0.05). The results using five different analytical approaches were similar. Sensitivity analyses showed no evidence of heterogeneity nor horizontal pleiotropy. According to the leave-one-out sensitivity analyses, no individual SNP was significantly influencing the causal effect of AR on cancers. Conclusions: These findings do not provide evidence to support that AR has a large impact on the risk of eight common cancers in the European population. However, we cannot rule out a very minor effect of AR on cancer. Further large-scale studies are necessary to validate our findings.